Spina bifida meningomyelocele is the major severely disabling birth defect in North America, but our knowledge of the factors responsible for neurobehavioral outcome is fragmentary. The program project aims to make these fragments coherent. The overall objective of this program project is to identify sources of variability-genetic, environmental, and CNS-that explain variations in the neurobehavioral outcomes of children with spina bifida meningomyelocele and hydrocephalus (SBH). To accomplish this objective, we propose to evaluate 583 children with spina bifida and 159 controls in five projects and three cores at two primary data collection sites: the University of Texas-Houston Medical School and the Hospital for Sick Children, Toronto. Project 1 (Genetics; Northrup, P.I.) evaluates genetic factors associated with spina bifida and related neural tube defects in Hispanic and Caucasian cohorts. Approximately 100 candidate genes will be tested and a genome-wide search will be initiated that permits testing of 150 of 330 possible markers. Projects 2 (Early Learning; Landry, P.I.) is a longitudinal study of infants with SBH from 7-36 months of age. This study addresses the relationship of core neurobiological deficits and the environment in producing early learning deficits in children with SBH. Project 3 (Cerebellum; Dennis, P.I.) evaluates the role of cerebellum/midbrain dysmorphology in producing the motor, spatial, and attentional deficits associated with SBH. Project 4 (Corpus Callosum; Hannay, P.I.) examines the corpus callosum anomalies characteristic of SBH in relationship to interhemispheric transmission and hemispheric specialization. Project 5 (Discourse and Academic Skills; Barnes, P.I. evaluates factors producing deficits in discourse, reading comprehension, and math in children with SBH. These 5 projects are supported by an Administrative Services Core (A; Fletcher, P.I.), Subject Recruitment and Evaluation Core (B; Fletcher, P.I.), and Database, Computer, and Statistics Core (C; Francis, P.I.) Core B provides for comprehensive medical, neuroimaging and psychometric evaluations of each child. Core C provides databases, project-specific data analyses, and overall data analyses. Altogether, this comprehensive program project should facilitate an integrated, multi-disciplinary understanding of spina bifida, a common and significantly handicapping disability.